Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Aging (Albany NY). 2020 Jun 17;12(12):11500-11516. doi: 10.18632/aging.103236.
Metastatic disease caused by castration-resistant prostate cancer (CRPC) is the principal cause of prostate cancer (PCa)-related mortality. CRPC occurs within 2-3 years of initiation of androgen deprivation therapy (ADT), which is an important factor of influencing PCa metastasis. Recent studies have revealed that non-coding RNAs in PCa can enhance metastasis and progression, while the mechanisms are still unclear. In this study, we reported that the long noncoding RNA-LINC00963 was increased in CRPC tissues and promoted migration of PCa cells in vitro and their metastasis in vivo. High levels of LINC00963 significantly decreased tumor suppressor miR-542-3p, whose levels in metastasis tissues were low compared to those in non-metastasis tissues. LINC00963 promotes and miR-542-3p inhibits metastasis. Furthermore, the expression levels of LINC00963 and miR-542-3p were positively and negatively associated with the expression of NOP2. We demonstrated that NOP2 promoted PCa by activating the epithelial-mesenchymal transition (EMT) pathway. For specific mechanism, dual luciferase reporter assays showed that miR-542-3p directly binds to both 3'-untranslated region (UTR) of LINC00963 and NOP2 mRNA. Taken together, our results show that LINC00963 acts as an inducer of PCa metastasis by binding miR-542-3p, thereby promoting NOP2. This axis may have diagnostic and therapeutic potential for advanced PCa.
去势抵抗性前列腺癌 (CRPC) 引起的转移性疾病是前列腺癌 (PCa) 相关死亡的主要原因。CRPC 在开始雄激素剥夺治疗 (ADT) 的 2-3 年内发生,这是影响 PCa 转移的重要因素。最近的研究表明,PCa 中的非编码 RNA 可以增强转移和进展,但其机制尚不清楚。在这项研究中,我们报道长非编码 RNA-LINC00963 在 CRPC 组织中增加,并促进 PCa 细胞在体外迁移和体内转移。高水平的 LINC00963 显著降低肿瘤抑制 miR-542-3p 的水平,转移组织中的 miR-542-3p 水平低于非转移组织中的水平。LINC00963 促进和 miR-542-3p 抑制转移。此外,LINC00963 和 miR-542-3p 的表达水平与 NOP2 的表达呈正相关和负相关。我们证明 NOP2 通过激活上皮-间充质转化 (EMT) 途径促进 PCa。对于特定机制,双荧光素酶报告基因检测显示 miR-542-3p 直接结合 LINC00963 和 NOP2 mRNA 的 3'-非翻译区 (UTR)。总之,我们的结果表明,LINC00963 通过结合 miR-542-3p 作为 PCa 转移的诱导剂,从而促进 NOP2。该轴可能对晚期 PCa 具有诊断和治疗潜力。